1. Field of the Invention
The invention relates to the production of antibiotic frenolicin B and its precursor deoxyfrenolicin.
2. Background
The biosynthesis of frenolicin, a compound of the structure ##STR1## was first reported in Antimicrob. Ag. Ann.-1960, 77:1961. Frenolicin was produced by cultivation of a soil isolate identified as Streptomyces fradiae under conventional agitation and aeration conditions. Frenolicin displayed antibiotic activity.
It was later reported that frenolicin could be chemically converted to deoxyfrenolicin, a compound of the structure ##STR2## by reduction with any of a variety of agents. (J,. Am. Chem. Soc., 88:4109, 1966; J. Am. Chem. Soc., 90:1325, 1968; U.S. Pat. No. 3,452,051).
The biosynthesis of deoxyfrenolicin was first reported in U.S. Pat. No. 4,199,514 and J. Antibiot., 31;959, 1978). These documents describe fermentation of a broth containing Streptomyces roseofulvus strain AM-3867 (ATCC No. 31476) carried out under aeration and aerobic conditions. Such fermentation produced a culture broth containing frenolicin, deoxyfrenolicin and an antibiotic frenolicin B having the chemical structure ##STR3##
After completion of the fermentation, the culture broth is separated into the bacterial cells and the filtrate. The filtrate of a culture broth produced by fermentation of a Streptomyces microorganism can be treated by conventional methods, such as by treatment with pH or temperature. (See Belter et al., Bioseparations--Downstream Processing for Biotechnology, J. Wiley & Sons, New York 1988, pp. 17, 25, 99, 105). However, previous procedures to separate and recover the antibiotics after completion of the fermentation described in U.S. Pat. No. 4,199,514 and J. Antibiot., 31:959, 1978 resulted in a recovery yield of frenolicin B of less than 50%.